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Investigation of Cell-Type Specific Contributions to Bladder Pain Modulation in the Central Amygdala

Award Number: F31DK121484
ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS
PERIOD OF PERFORMANCE START DATE: 01/19/2019
PERIOD OF PERFORMANCE END DATE: 09/27/2021

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Investigation of Cell-Type Specific Contributions to Bladder Pain Modulation in the Central Amygdala - Project Summary Urologic chronic pelvic pain (UCPP) syndromes are the most common chronic visceral pain conditions, affecting between 5 and 10 million people in the United States. The lack of effective treatments for UCPP is likely due, in part, to a failure to understand the central nervous system's contribution to the modulation of the disease. Recent evidence has implicated the central nucleus of the amygdala as an important region in the pathology of bladder pain. Evidence from both human and rodent models indicates that the left and right amygdala have different contributions to the modulation of pain. UCPP patients exhibit lateralized changes in amygdala functional connectivity compared to healthy patients and patients suffering from other visceral pain conditions. Recently, the right and left central amygdala has been shown to have divergent functions in the context of bladder pain in mice. We aim to further explore this lateralization in order to determine molecular modulators responsible for driving these differential functions. Calcitonin gene related peptide (CGRP) is a neuropeptide that separately has been shown to have both pro- and anti-nociceptive functions in the central amygdala. Our preliminary data indicates that CGRP activity shows interesting asymmetries in the context of bladder pain, with CGRP in the right central amygdala driving bladder pain but CGRP in the left central amygdala blocking bladder pain. The goal of this proposal is to understand how CGRP contributes to the differential modulation of bladder pain in the left and/or right central amygdala. We will approach this goal by 1) exploring the influence of brainstem CGRP-expressing projections in the central amygdala on the physiological response to bladder stimulation and 2) investigating the contribution of these same CGRP cells on the modulation of pain-like behavior in awake animals using a mouse model of inflammatory bladder pain. These experiments will not only help determine the extent of CGRP in the differential processing of bladder pain by the left and right central amygdala but also provide a better understanding of a contributing mechanism to UCPP and therefore open the door for more advanced and effective CNS targeted therapies for patients.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2023 ( Subtotal = -$24,541 )
2023	2021	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVENUE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	11/23/2022	NON-COMPETING CONTINUATION	-$24,541
														Subtotal = -$24,541

Issue Date FY: 2022 ( Subtotal = -$7,966 )
2022	2021	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE	PITTSBURGH	PA	15282	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/15/2021	NON-COMPETING CONTINUATION	-$7,966
														Subtotal = -$7,966

Issue Date FY: 2021 ( Subtotal = $43,246 )
2021	2021	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE STE 205	PITTSBURGH	PA	15219	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	3	12/2/2020	NON-COMPETING CONTINUATION	$42,730
2021	2021	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE STE 205	PITTSBURGH	PA	15219	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	3	2/8/2021	NON-COMPETING CONTINUATION	$516
														Subtotal = $43,246

Issue Date FY: 2020 ( Subtotal = $42,730 )
2020	2020	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE STE 205	PITTSBURGH	PA	15219	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	2	12/19/2019	NON-COMPETING CONTINUATION	$42,226
2020	2020	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE STE 205	PITTSBURGH	PA	15219	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	2	2/14/2020	NON-COMPETING CONTINUATION	$504
														Subtotal = $42,730

Issue Date FY: 2019 ( Subtotal = $42,226 )
2019	2019	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE STE 205	PITTSBURGH	PA	15219	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	000	1	1/10/2019	NEW	$42,226
2019	2019	DUQUESNE UNIVERSITY OF THE HOLY SPIRIT	600 FORBES AVE STE 205	PITTSBURGH	PA	15219	ALLEGHENY	USA	Diabetes, Digestive, and Kidney Diseases Extramural Research	001	1	1/10/2019	NEW	$0
														Subtotal = $42,226

Grand Total All Awards = $95,695

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Investigation of Cell-Type Specific Contributions to Bladder Pain Modulation in the Central Amygdala

Award Number: F31DK121484

ORGANIZATION: NATIONAL INSTITUTE OF DIABETES & DIGESTIVE & KIDNEY DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: FELLOWSHIP/SCHOLARSHIP/STUDENT LOANS

PERIOD OF PERFORMANCE START DATE: 01/19/2019

PERIOD OF PERFORMANCE END DATE: 09/27/2021

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